An enzyme activity as a potential biomarker for Alzheimer's disease.

Research output: Contribution to journalPublished meeting abstract


Background: Six different N-terminal amyloid precursor protein (APP) fragments, with molecular weight ∼12 kDa, have previously been identified in human cerebrospinal fluid (CSF). In a pilot study, both the sum of their concentrations, measured by western blot, and the relative abundance pattern, measured by mass spectrometry, were different in Alzheimer's disease (AD) patients compared to healthy controls. To test if these differences were also reflected in protease activities that possibly give rise to the ∼12 kDa fragments an enzymatic assay was developed and the activity in CSF was investigated for its potential as a biomarker for AD. Methods: The substrate in the protease activity assay was a custom made fluorochrome/quencher labeled peptide that covers the cleavage sites in APP (APP118-APP127) corresponding to the C-termini of the six ∼12 kDa APP fragments. The activity was measured in CSF from 55 AD patients and 17 controls. Results: There was a significant increase in the protease activity in CSF from AD patients compared to the controls (p = 0.001). This is in line with previous results which indicate that the sum of the ∼12 kDa fragments are elevated in AD. Results from inhibition studies strongly suggests that the enzyme responsible for the cleavage of the substrate is an aspartic protease since a sub nM IC50 value was recorded for Pepstatin A while no inhibition was observed for the cysteine protease specific inhibitor E64 at concentrations up to100 nM. Conclusions: There exists an enzymatic activity in CSF capable of cleaving a peptide substrate that spans a portion, close to the N-terminal, of APP. In a pilot study the activity is increased in AD patients compared to controls suggesting that it can be used as a biomarker.


External organisations
  • Skaraborg Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Pages (from-to)S497–S498
JournalAlzheimer's & Dementia
Issue number4
Publication statusPublished - 2010
Publication categoryResearch
EventAlzheimer's Association International Conference on Alzheimer's Disease 2010 - Honolulu, United States
Duration: 2010 Jul 102010 Jul 15

Related projects

Per Johansson

1999/01/01 → …

Project: ResearchClinical research

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